Choriocarcinoma in situ at a first trimester

Two cases of choriocarcinoma in situ arising in a first trimester placenta are reported in a 28-year-old gravida 2, para 1, Japanese woman and a 38-year-old gravida 2, para 0. Both had a dilation and curettage (D and C) for vaginal bleeding and the absence of intrauterine fetus. No macroscopic abnormalities were noted in either case. However, histologically, localized nodules of neoplastic trophoblastic proliferation measuring 5 mm in the first case, and 6 mm in the second appeared to arise directly from normal stem villi and project into the intervillous space. Both tumours were composed of biphasic cytotrophoblast and syncytiotrophoblast. Fetal elements were not observed in either case. Radiographic studies showed no metastatic lesions in either patient. Urinary human chorionic gonadotropin levels were within normal range in both patients. The first patient had a normal full-term spontaneous vaginal delivery 22 months after the D and C and was free from disease without therapy at 32 months. The second patient was free from disease without therapy with a limited follow-up. These tumours provide evidence for an origin of choriocarcinoma from trophoblast of a stem villus. This report illustrates the need to perform thorough microscopic examination of the products of conception especially in the absence of a fetus or fetal parts.     

MRI evaluation of the diaphragmal opening: using MRI parallel to the transsphenoidal surgical approach.

Twenty-six adult diaphragma sellae and infundibulae were examined by MRI parallel to the transsphenonidal surgical plane with attention given to the diaphragmal opening. The diaphragmal opening was observed in 11 cases (42.3%). The anteroposterior diame ter of the opening ranged from 4.0 to 14.0 mm (mean 8.8 mm), and the lateral diameter ranged from 6.0 to 14.0 mm (mean 9.5 mm). In the cases of open diaphragma sellae, the infundibulum tended to be located in the posterior part of the diaphragma sellae but this was not statisticallysignificant. On MRI parallel to the transsphenoidal surgical approach, the anatomy of the dia phragma sellae was well evaluated.     

Changes in middle ear pressure in daily life

The present study was performed to estimate changes of middle ear pressure (ME-P) during actions of daily life such as nose blowing and sniffing. ME-P was measured in 18 patients with perforation of the eardrum. They were asked to perform actions which included nose blowing and sniffing. Eustachian catheterization and politzerization were also applied. Change of ME-P before and after these actions was recorded using a pressure monitor. Results showed that changes of ME-P after nose blowing with both nostrils closed were large and rapid. The mean value of ME-P after nose blowing was 252 mmH₂O. In our previous study, the mean value of cerebrospinal fluid pressure (CSF-P) after nose blowing was 388 mmH₂O.¹ Therefore, the pressure gradient across the cochlear windows is about 130 mmH₂O during nose blowing. The cochlear windows may have been pressed toward the middle ear side. After sniffing, ME-P was unchanged. These results suggest that nose blowing may be an important cause of perilymphatic fistula (PLF) via the “explosive route,”² while sniffing is not likely to cause PLF.     

Phase II study of paclitaxel (BMS-181339) intravenously infused over 3 hours for advanced or metastatic breast cancer in Japan

A Phase II study of paclitaxel in patients with primary advanced or metastatic breast cancer was conducted by a cooperative study group consisting of 16 institutions in Japan. Paclitaxel at a dose of 210 mg/m2 was intravenously infused over 3 hours, along with premedication to prevent hypersensitivity reactions. The course was repeated at 21-day intervals. Of 62 eligible patients, 60 were evaluable for toxicity and 59 were evaluable for efficacy. Forty-five patients were previously treated with anthracyclines. Twenty-one of 59 patients (35.6%) had a major objective response including 2 CRs and 19 PRs (95% confidence interval, 23.6–49.1%). A response rate of 35.5% (CR1, PR10) was observed in 31 patients refractory to the anthracyclines containing prior metastatic chemotherapy. Median (range) time was 41 (6–100) days to onset of and median duration of response was 125 (36–305) days. Toxicities included leukopenia (grade 3, 4: 67%), anemia (grade 1–3: 80%), thrombocytopenia (grade 1: 8%), alopecia (grade 3: 43%), peripheral neuropathy (grade 1–3: 93%), arthralgia (59%), myalgia (46%), nausea and vomiting (40%), fever (33%), allergic reaction (grade 3: 2%) and hypotension (grade 3: 5%). All toxicities were tolerable and manageable. Paclitaxel intravenously infused over 3 hours demonstrated a significant antitumor activity for metastatic breast cancer. Furthermore, paclitaxel exhibited non-cross resistance to anthracycline. Paclitaxel administered as a convenient 3-hour infusion is effective for patients with metastatic breast cancer and has an acceptable toxicity profile.     

Alteration of proteins regulating apoptosis, Bcl-2, Bcl-x, Bax, Bak, Bad, ICH-1 and CPP32, in Alzheimer''s disease

Recently, apoptosis has been implicated in the selective neuronal loss of Alzheimer's disease (AD). Apoptosis is regulated by the B cell leukemia-2 gene product (Bcl-2) family (Bcl-2, Bcl-x, Bax, Bak and Bad) and the caspase family (ICH-1 and CPP32), with apoptosis being prevented by Bcl-2 and Bcl-x, and promoted by Bax, Bak, Bad, ICH-1 and CPP32. In the present study, we examined the levels of these proteins in the membranous and cytosolic fractions of temporal cortex in AD and control brain. In the membranous fraction, the levels of Bcl-2, Bcl-x_L, Bcl-x_β, Bak and Bad were increased in AD. In the cytosolic fractions, the level of Bcl-x_β was increased, while Bcl-x_L, Bax, Bak, Bad and ICH-1_L were unchanged. CPP32 was not detected in AD or control brain. These findings demonstrate a differential involvement of cell death-regulatory proteins in AD and suggest that Bak, Bad, Bcl-2 and Bcl-x are upregulated in AD brains.     

Long-term effect of radical gastrectomy on nutrition and immunity

The long-term effects of gastrectomy on the nutritional and immunologic status were prospectively studied in 79 gastric cancer patients who underwent curative gastrectomy and were followed by us after operation for an average of 5 years and 3 months. The percent of actual weight to pre-illness normal weight was lower than 95% in 80% of all study patients. Retinol binding protein, prealbumin, and albumin were lower than normal in 17%, 26%, and 26% of the patients, respectively. The mean values of the percent normal weight, retinol binding protein, and prealbumin were significantly lower in the totally gastrectomized patients than in the subtotally gastrectomized ones (P<0.01). The procedures of reconstruction did not affect the nutritional status except for the prealbumin level which was significantly decreased in Roux-en-Y cases than in interposed cases of totally gastrectomized patients. Cell-mediated immunological alterations after gastrectomy were observed in 31%, 37%, and 71% of all patients for OKT3 subpopulation, OKT4/OKT8 ratio, and blastogenesis by phytohemagglutinin, respectively. A multivariate analysis revealed that the long-term immunity of the gastrectomized patients after operation was not affected by the levels of albumin and rapid turnover proteins but by the splenectomy and weight loss they underwent.     

Suppressive effect of FK-506, a novel immunosuppressant, against MPTP-induced dopamine depletion in the striatum of young C57BL/6 mice

Systemic injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to damage the dopaminergic nigrostriatal system in C57BL/6 mice. We have investigated the effects of immunosuppressants, FK-506 and cyclosporin A (CsA), on MPTP-induced dopamine (DA) depletion in the striatum of young C57BL/6 mice. 10 days after MPTP treatment (25 mg/kg i.p. given daily, 5 days), DA in the striatum was depleted by 80%. However, pretreatment with FK-506, a novel immunosuppressant, significantly protected MPTP-induced DA depletion in the striatum, but FK-506 itself did not affect the DA content. CsA, another immunosuppressant, also protected MPTP-induced DA depletion. From these results can be seen that immunosuppressants seem to inhibit MPTP neurotoxicity toward nigrostriatal dopaminergic neurons of young C57BL/6 mice.     

Acute-phase kidney transplants show early peak appearance in Tc-99m DTPA renogram

Kidney transplants have been evaluated using a radionuclide technique to determine perfusion index (PI), mean transit time (MTT), and the parameters in renogram curve (Tmax, T1/2, and T2/3). The values for Tmax, T1/2, and T2/3 were also determined in normal volunteers. The results indicated that the Tmax value was less than 2 minutes, one week after transplantation. The other data were within normal limits. The appearance of Tmax was very early. The early time activity curve (TAC) was quite similar to the blood disappearance curve, TAC did not have the functional-phase, so-called, 2nd-phase. These data suggested that there could be an abnormality of the renal circulation in the transplanted kidney. The suggestion offers the new finding in a field of renal transplantation using radionuclide technique.     

Adenovirus-mediated gene transfer of triple human complement regulating proteins (DAF, MCP and CD59) in the xenogeneic porcine-to-human transplantation model

In this study, the adenovirus-mediated gene transfer of triple human complement regulating proteins was investigated in xenogeneic pig liver perfusion. The porcine liver was perfused in situ at 4 degrees C under a pump-driven veno-venous shunt of the portal vein and inferior vena cava, with 5 to 15x10(11) plaque-forming units (pfu) of adenovirus vector (group 1: AxCALacZ; 2: AxCACD59; 3: AxCACD59 + AxCADAF; 4: AxCACD59 + AxCADAF + AxCAMCP) for 1 h (for each, n=3). The livers were harvested 24 h after gene transfer and then were reperfused ex-vivo with fresh human blood for 2 h. In immunohistochemical staining, each complement regulating protein (CRP) showed a distribution similar to that of the LacZ expression. The C3 levels in the perfusate were also maintained at higher levels in group 4 from 60 to 120 min after reperfusion (C3: 85% to 95% of the initial level) than in groups 1 to 3 (C3: 80% to 90% of the initial level) from 60 to 120 min after reperfusion. The complement deposition on the porcine liver [C3, membrane attack component (MAC)] decreased significantly more in group 4 than in groups 1 to 3. In conclusion, the adenovirus-mediated multiple gene transfer of human CRPs (hCRPs) was found to effectively suppress the complement activation in xenogeneic pig liver perfusion.